Knisley S B, Grant A O
Division of Cardiovascular Disease, University of Alabama at Birmingham 35294-0019, USA.
J Mol Cell Cardiol. 1995 May;27(5):1111-22. doi: 10.1016/0022-2828(95)90047-0.
Strong defibrillation-type electric field stimulation may injure myocytes when transmembrane potentials during the pulse exceed the threshold for membrane permeabilization. The location of injury may depend on intrinsic transmembrane potential or influx of calcium by "electro-osmosis" during the stimulation pulse in addition to the transmembrane potential changes induced by the pulse. We have studied injury by examining contracture and changes in transmembrane potential-sensitive dye fluorescence induced by electric field stimulation (St) with a duration of 20 ms and strength of 16-400 V/cm in isolated rabbit ventricular myocytes. St of 100-150 V/cm produced injury in myocytes oriented parallel to the St field frequently without injuring myocytes oriented perpendicular to the field. Injury required calcium in the solution and was asymmetric, occurring first at the myocyte and facing the St anode in 100% of injured myocytes in normal Tyrode's solution. Injury depended significantly on whether the product of the electric field strength and myocyte length exceeded a threshold of 1.1 V (P < 0.05). Asymmetric injury at the end facing the anode was still present in 96% of injured myocytes for stimulation after depolarization by an action potential or 20 mM or 125 mM potassium, suggesting that intrinsic transmembrane potential is not responsible for asymmetry. In 125 mM potassium, eliminating calcium from the bathing solution during the St pulse and introducing calcium after the pulse decreased the fraction of injured myocytes in which injury occurred at the end facing the anode to 62%, suggesting that calcium influx by "electro-osmosis" at the myocyte end facing the anode contributes to asymmetry. Asymmetric injury at the end facing the anode was still present in 100% of injured myocytes after adding 1 mM tetraethylammonium chloride, indicating that asymmetry is not sensitive to the potassium channel blockade. For stimulation pulses stronger than 50 V/cm given after depolarization by an action potential, transmembrane potentials at both myocyte ends decayed after the initial deflection indicating that permeabilization occurred at both ends. In conclusion, injury depends on myocyte orientation and is asymmetric occurring first at the myocyte end facing the anode. Asymmetric injury is not explained by asymmetric permeabilization, is independent of the intrinsic transmembrane potential and may result from "electro-osmosis" during the stimulation pulse.
当脉冲期间的跨膜电位超过膜通透性阈值时，强除颤型电场刺激可能会损伤心肌细胞。损伤的位置可能取决于内在跨膜电位，或刺激脉冲期间通过“电渗作用”导致的钙内流，此外还取决于脉冲引起的跨膜电位变化。我们通过检测离体兔心室肌细胞中由持续时间为20毫秒、强度为16 - 400伏/厘米的电场刺激（St）诱导的挛缩和跨膜电位敏感染料荧光变化来研究损伤情况。100 - 150伏/厘米的St刺激经常会使与St场平行排列的心肌细胞受损，而不会损伤与场垂直排列的心肌细胞。损伤需要溶液中有钙，并且是不对称的，在正常台氏液中，100%受损心肌细胞的损伤首先发生在心肌细胞面向St阳极的一端。损伤显著取决于电场强度与心肌细胞长度的乘积是否超过1.1伏的阈值（P < 0.05）。在动作电位、20毫摩尔或125毫摩尔钾引起去极化后进行刺激时，96%受损心肌细胞在面向阳极的一端仍存在不对称损伤，这表明内在跨膜电位并非不对称损伤的原因。在125毫摩尔钾溶液中，在St脉冲期间去除浴液中的钙并在脉冲后引入钙，可使损伤发生在面向阳极一端的受损心肌细胞比例降至62%，这表明在面向阳极的心肌细胞一端通过“电渗作用”导致的钙内流促成了不对称性。添加1毫摩尔氯化四乙铵后，100%受损心肌细胞在面向阳极的一端仍存在不对称损伤，这表明不对称性对钾通道阻断不敏感。对于动作电位去极化后给予的强度大于50伏/厘米的刺激脉冲，心肌细胞两端的跨膜电位在初始偏转后均衰减，表明两端均发生了通透性改变。总之，损伤取决于心肌细胞的取向，是不对称的，首先发生在心肌细胞面向阳极的一端。不对称损伤不能用不对称通透性来解释，与内在跨膜电位无关，可能是刺激脉冲期间“电渗作用”的结果。
